Molecular genetic parameters in pathogenesis and prognosis of testicular germ cell tumors

Aim of this review article was to critically analyze the recently described cytogenetic and molecular markers for testicular germ cell tumors with reg ard to their clinical utility. The isochromosme i(12p) represents the most common and characteristic cytogenetic finding which already appears in test icular carcinoma in situ. A number of proto-oncogenes (cyclin D and PTHLH) as well as putative tumor suppressor genes are localized on 12p; however, t heir role in pathogenesis and prognosis of testicular germ cell tumors has not been defined yet. Clinical characteristics of patients with familial te sticular germ cell tumors indicate a genetic background for the development of testicular tumors. Although a number of chromosomal loci encoding poten tial testicular tumor susceptibility genes have been identified, the geneti c basis of testicular cancer pathogenesis is sti II unknown. With regard to molecular prognostic risk factors most of the reported data on proliferati on markers, tumor suppressor genes, proteases and adhesion molecules have t o be confirmed in prospective randomized trials prior to their widespread c linical use. Based on the available data on prospective studies the percent age of embryonal carcinoma and vascular invasion appear to be the most sign ificant prognosticators. Investigation and identification of those factors determining the aggressive biologic behavior of embryonal carcinoma compare d to all other histological components appear to be most promising in the r esearch for prgnosticators of metastatic disease. In conclusion, the increa sing knowledge of molecular genetic events involved in pathogenesis and pro gnosis of testicular germ cell tumors will not only help to better understa nd development and progression of testicular cancer, but it will also defin e new approaches to classification and management of germ cell tumors. Copy right (C) 2000 S. Karger AG, Basel.